Tumor necrosis factor receptor (TNFR)-associated factor 2A (TRAF2A), a TRAF2 splice variant with an extended RING finger domain that inhibits TNFR2-mediated NF-kappaB activation.
We describe here the identification and characterization of tumor necrosis factor receptor (TNFR)-associated factor 2A (TRAF2A), a splice variant of the TRAF2 molecule utilized for signal transduction by members of the TNFR family. TRAF2A and TRAF2 cDNAs are identical in sequence with the exception of an extra 21 base pairs of sequence encoding a 7-amino acid insert within the TRAF2A RING finger domain. TRAF2A mRNA expression is regulated in a tissue-specific manner, with relative TRAF2A mRNA levels being highest in spleen and lowest in brain. TRAF2A protein is capable of binding to the cytoplasmic domain of TNFR2 (p75) and is detectable in T-lymphoma cells stably transfected with the TRAF2A cDNA. Unlike TRAF2, TRAF2A has a short half-life ( approximately 100 min) in these cells and is expressed at only low levels in transiently transfected COS-7 cells. However, TRAF2A levels in transiently transfected COS-7 cells approach those of TRAF2 upon coexpression with TRAF1 and/or TRAF2, indicating that TRAF2A stability is regulated by the binding of other TRAF family proteins. Also in contrast to TRAF2, TRAF2A is unable to stimulate NF-kappaB activity when overexpressed in 293 cells and acts as a dominant inhibitor of TNFR2-dependent NF-kappaB activation. TRAF2A thus represents a novel signal transduction protein, the expression of which can act to inhibit TRAF2-dependent NF-kappaB activation.
Brink
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Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA. R.Brink@centenary.usyd.edu.au
Lodish
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HF
D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D005786:Gene Expression Regulation / Q000235:genetics; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000502:physiology; D047992:TNF Receptor-Associated Factor 2; D014162:Transfection / Q000235:genetics
D016328:NF-kappa B; D011506:Proteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D047992:TNF Receptor-Associated Factor 2